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Wednesday, January 20, 2010
hypothesis: Pretreatment with alternate day modified fast will permit higher dose and frequency of cancer chemotherapy and better cure rates
Johnson JB, John S, Laub DR (2009) Pretreatment with alternate day modified fast will permit higher dose and frequency of cancer chemotherapy and better cure rates. Med Hypotheses.72(4):381-2
Abstract
It is established that calorie restriction (CR) increases the resistance of cells to various stressors such as oxidative damage, excitotoxins, mercury and acetaminophen. Alternate day feeding (ADF) may confer greater stress resistance than daily CR of 30% or 40%. A recent study in three strains of mouse showed that a fast of 48 or 60 h prevented toxic effects due to administration of doses 2-4 times the maximum human dose of etoposide, a chemotherapy agent which acts through increased oxidative stress. In addition, mice inoculated with neuroblastoma survived longer when pretreated with fasting, then given high dose etoposide, as well as not exhibiting toxicity. This increased survival was construed as evidence of differential stress resistance between normal and cancer cells, the cancer cells being only partially protected by the pretreatment fast. In clinical practice, increased differential stress resistance could lead to the use of much higher doses of chemotherapy agents, and in the absence of toxicity, make it possible to repeat the treatment to kill residual cancer cells. Humans are unlikely to comply with a total fast of longer than 24 or 48 h, which may be insufficient to activate the same gene expression process. Based on published data we estimate that an optimal time period for development of stress resistance is 2-3 weeks when alternate day feeding is employed. Our previously published experience suggests that 2-3 weeks of alternate day modified fast in which subjects eat ad libitum one day and <20% of one's estimated caloric requirement the next will confer a similar stress resistance. Compliance with this diet is high and greater maintenance of body weight is feasible. We hypothesize that a pretreatment of 2-3 weeks with the alternate day modified fast will improve outcomes in cancer chemotherapy, decreasing morbidity and raising cure rates.
From ScienceNews.org: Possible anticancer power in fasting every other day
http://www.sciencenews.org/view/generic/id/40242/title/Possible_anticancer_power_in_fasting_every_other_day
Fasting every other day reduces some hallmarks of cancer in mice, even when the mice voraciously consume high-fat food between fasts, a study in an upcoming Nutrition shows.
Scientists have known for decades that eating fewer calories — roughly 25 to 50 percent less than recommended — extends life span in animals ranging from worms to dogs. But, “caloric restriction on a daily basis is very hard,” says Eric Ravussin, a physiologist at the Pennington Biomedical Research Center in Baton Rouge, La., who studies caloric restriction.
Last year, researchers including Krista Varady, then of the University of California, Berkeley, published a study suggesting that a less drastic version of caloric restriction provides a constellation of health benefits in mice. Called alternate-day fasting, the regimen of eating as much food, low-fat in this study, as one wants one day but fasting the next confers some of the same anticancer benefits as just cutting calories at a constant rate, the team found.
But for people, eating a low-fat diet one day and fasting the next is still challenging. Varady and her colleagues wanted to know whether the diet could be made easier to swallow and still provide similar benefits.
In the new study, Varady and other researchers compared mice who fasted every other day, both on high-fat and low-fat diets, to mice that didn’t fast but instead ate a low-fat diet every day. The mice on the ultimate yo-yo diet ate high-fat food, in which 45 percent of the calories came from fat — comparable, Varady says, to human diets of fast food and processed food.
On the fasting days, mice were fed 15 percent of their required calories from either the high- or low-fat food.
The results were surprising, says Varady. Mice that ate the rodent equivalent of Big Macs every other day showed the same anticancer benefits of fasting as the mice that ate the low-fat diet every other day. High rates of cell division — a key feature of cancer — were lower in the mice who fasted every other day than in mice that had not fasted. Mice who fasted every other day also had reduced levels of IGF-1, a protein that induces cell growth and has been linked to cancer.
The new study on mice is the “next installment in a systematic and interesting series of studies” from the researchers, comments James Johnson, a doctor affiliated with the Louisiana State University Health Sciences Center and studies alternate-day fasting in humans.
The option to eat high-fat meals while fasting every other day may make people more likely to stick with the demanding diet regimen, researchers say. To date, only three small studies have examined the effects of alternate-day fasting on people, says Varady, now at the University of Illinois in Chicago.
She says the next step is to see whether an unrestricted high-fat diet one day and a small amount of food the next will confer the same health benefits in humans as it does in mice. Varady and her colleagues are currently conducting a study to test whether humans are able to stick with such a diet. Preliminary data suggest that they can.
“The alternate diet has a lot of potential,” comments Valter Longo, a University of Southern California in Los Angeles researcher who studies aging. But, he adds, “I seriously doubt that very many people would adopt it because it is very tough to do regularly.”
Ravussin knows the difficulty firsthand. When he attempted alternate-day fasting himself, he reported feeling very irritable and hungry. “My wife told me, ‘Don’t do it again.’ ”